Breast cancer is the most common cancer among women in the United States. Despite advances in the early detection and treatment of breast cancer, it remains the second most common cause of cancer death among women. Treatment of metastatic (Stage IV) breast cancer remains palliative, and new treatments are urgently needed. Paclitaxel is one of the most single active agents in the treatment of metastatic breast cancer, with reponse rates of over 50% in some Phase II trials. Losoxantrone is an investigational anthrapyrazole DNA intercalating anticancer agent which is in Phase III clinical trials, and has shown response rates up to 45% in Phase II trials in patients with metastatic breast cancer. The current study is an industry sponsored, multicenter, randomized, open-label comparative study between paclitaxel alone vs. the combination of paclitaxel and losozantrone, with G-C SF support in order to maintain drug dose intensity and improve the safety profile. Patients will be randomized in a ratio of 1:2 to paclitaxel alone vs. losozantrone/palitaxel/G-C SF. A total of 300 patients is planned to be entered at approximately 50 sites.